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PPARD is a critical inhibitor of cartilage growth in external ears

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Sus scrofa

PROVIDER: GSE92374 | GEO | 2017/06/09

SECONDARY ACCESSION(S): PRJNA357365

REPOSITORIES: GEO

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PPARD is an Inhibitor of Cartilage Growth in External Ears.

Project description:Peroxisome proliferator-activated receptor beta/delta (PPARD) is an important determinant of multiple biological processes. Our previous studies identified a missense mutation in the PPARD gene that significantly reduces its transcription activity, and consequently causes enlarged external ears in pigs. However, the mechanisms underlying the causality has remained largely unknown. Here, we show that PPARD retards the development of auricular cartilage by accelerating the apoptosis of cartilage stem/progenitor cells (CSPCs), the terminal differentiation of cartilage cells and the degradation of cartilage extracellular matrix in the auricle. At the transcription level, PPARD upregulates a set of genes that are associated with CSPCs apoptosis and chondrogenic differentiation, chondroblast differentiation and extracellular matrix degradation. ChIP-seq identified direct target genes of PPARD, including a well-documented gene for cartilage development: PPARG. We further show that compared to wild-type PPARD, the G32E mutant up-regulates the expression of PPARG and subsequently leads to the downregulation of critical genes that inhibit cartilage growth. These findings allow us to conclude that PPARD is an inhibitor of auricular cartilage growth in pigs. The causative mutation (G32E) in the PPARD gene attenuates the PPARD-mediated retardation of cartilage growth in the auricle, contributing to enlarged ears in pigs. The findings advance our understanding of the mechanisms underlying auricular development in mammals, and shed insight into the studies of innate pinna disorders and cartilage regeneration medicine in humans.

| S-EPMC5441183 | biostudies-literature

PPARD is a critical inhibitor of cartilage growth in external ears [RNA-Seq]

Project description:In this study, we uncover the molecular mechanism that PPARD transactive-deficient pigs have large-eared feature. Evidently from this work, PPARD plays a vital role on inhibiting cartilage growth by regulating the transcription of critical genes for chondrogenesis in ligand dependent manner; the activation of sPPARD speeds up apoptosis in CSPCs, terminal differentiation of chondroblasts and matrix degradation in auricular cartilage. The transactive-deficient PPARD has not the capability to slow down cartilage growth and consequently causes that ear size of carried animals increases at a high growth rate. As the role of PPARD in cartilage is similar in pigs, mice and humans, and since cartilage development is well-conserved in animals, our data helps to better understanding of cartilage development and treatment of cartilage-related diseases.

2017-06-09 | GSE92373 | GEO

PPARD is a critical inhibitor of cartilage growth in external ears [ChIP-Seq]

2017-06-09 | GSE92370 | GEO

PPARD is a critical inhibitor of cartilage growth in external ears

Project description:PPARD is a critical inhibitor of cartilage growth in external ears

| PRJNA357365 | ENA

Combinatorial treatment of DNMT inhibitor and LSD1 inhibitor results in cell growth inhibition and reexpression of epigenetically silenced genes